Nausea and vomiting are serious problems frequently observed in patients receiving a cancer chemotherapeutic agent and radiotherapy. Therefore control of nausea and vomiting is a very important auxiliary treatment for undergoing satisfactory treatment for cancer. Gralla, R. J. et al have reported in N. Engl. J . Med. 305, 905-909 (1981) that nausea and vomiting are effectively prevented by intravenous administration of metoclopramide at high dose . However it has been revealed that presently available antiemetics, particularly compounds containing a benzamide structure are associated with adverse reactions such as sedation, ataxia, diarrheas and tasikinesia due to their dopamine-blocking activities and central nerve-depressant activities.
Cunningham, D. et al have reported in The Lancet, 1, 1461-1463 (1987) that specific antagonists of 5-HT.sub.3 receptors prevent vomiting and nausea associated with cancer therapy. Thus 5-HT.sub.3 receptor antagonists are believed to be anti-emetics which can prevent vomiting and nausea at a lower dose than known agents without adverse reactions associated.
As 5-HT.sub.3 receptor antagonists, compounds containing an azabicyclic moiety are known as disclosed in U.S. Pat. Nos. 4,789,673; 4,803,199; 4,910,207; GB 2152049 A; U.S. Pat. No. 4,800,225, GB 2208862 A and European Patent Application 0377967 A2 and compounds containing an imidazole moiety are known as disclosed in GB 2153821 A.
Under such circumstances, it has been desired to develop more selective antagonists of 5-HT at 5-HT.sub.3 receptors .